Due to the portability of inhaled preparations and better patient compliance, inhalation administration has become the most commonly used mode of administration after oral administration, and more and more attention and approval have been paid to the inhalation administration route. For patients with lung disease, compared with other modes of administration, inhaled administration can achieve higher local drug concentration and reduce systemic adverse effects. The latest research found that inhaled administration has played an important role in improving the clinical treatment of patients with new coronary pneumonia.
The COVID-19 outbreak has brought huge challenges to global public health
The outbreak of COVID-19 has brought huge challenges to global public health. Up to now, there is still no specific therapeutic agent for the virus, and we urgently need new effective intervention strategies to combat this disease. Recently, TheLancet published an article on the latest clinical trial for the treatment of COVID-19. The results of the trial show that the aerosol inhalation of IFN-κ+TFF2 is expected to improve the clinical treatment of patients with moderate COVID-19.
01 Latest Finding
Previous clinical trials have shown that type I interferons (such as IFN-α, IFN-β) can effectively inhibit the replication of SARS-CoV-1, thereby reducing clinical complications. However, IFN-α/β can induce a large influx of pathogenic inflammatory monocytes and vascular leakage to cause persistent inflammation. Therefore, systemic adverse reactions of IFN-α/β will also be a problem.
IFN-κ is a relatively mild type I interferon, which can effectively inhibit the replication of enveloped viruses by activating the signal transduction pathway of interferon-stimulated response elements. Trefoil factor 2 (TFF2) is a secreted polypeptide with three disulfide bonds, which can protect the gastrointestinal tract from microbial or chemical damage by promoting the repair of damage and regulating the immune response.
Based on these findings, the researchers hypothesized that the combined administration of human-derived IFN-κ and TFF2 may synergistically combat SARS-CoV-2 induced respiratory pneumonia by reducing virus replication, reducing inflammation, and improving respiratory tract remodeling, thereby improving COVID- Prognosis of 19 patients. Therefore, in order to evaluate the efficacy and safety of aerosol inhalation of TFF2 and IFN-κ protein on SARS-CoV-2 infection, the researchers conducted a survey of adult patients hospitalized with moderate COVID-19 disease at the Shanghai Public Health Clinical Center. An open-label, non-randomized clinical trial.
02 Test Method
From February 1, 2020 to April 6, 2020, a total of 33 COVID-19 patients with moderate disease symptoms were recruited, 11 patients were assigned to the experimental group, and the remaining 22 patients received only standard supportive care and were Classified as a control group. The nebulized drug is made of purified mature TFF2 and IFN-κ proteins. These proteins are produced under Good Manufacturing Practice (GMP) conditions with a purity of over 99%, and the biological activities of these two proteins have been verified in vitro. Both proteins were dissolved in 5 mL of sterile water, and the aerosol was delivered for 20-30 minutes through a nasal mask driven by a medical compressed air atomizer (YUWELL, 403M). Aerosol inhalation treatment started on the first day of hospitalization and received 3 aerosol treatments every 48 hours.
03 Test Data
According to the above data, it can be seen that IFN-κ+TFF2 treatment has no obvious negative effects on liver, gallbladder and platelets.
The absolute count of total white blood cells (WBC) in the IFN-κ+TFF2 group on day 4 was significantly higher than that of the control group. After the treatment is completed (from day 6 to day 10), the white blood cell level returns to the normal range. This indicates that the administration of IFN-κ+TFF2 may reduce lung inflammation, thereby interrupting the migration of white blood cells and leading to accumulation in the blood. In addition, the blood CRP level of the IFN-κ+TFF2 group was much lower than that of the control group, further indicating that the experimental group produced less inflammation and stress response. In addition, there was no significant difference in the number of lymphocytes and hemoglobin concentration between the two groups, which indicated that IFN-κ+TFF2 had no effect on lymphocyte survival and red blood cell function.
The above is an analysis of several clinical data of cough relieving, CT imaging improvement, virus negative time and hospital stay. It can be seen that in the IFN-κ+TFF2 group, the cough was relieved compared with the control group, the CT imaging improved earlier and the hospital stay was shortened.
04 Test Results
This open-label non-randomized clinical trial found that aerosol inhalation of IFN-κ+TFF2 is a safe treatment for patients with moderate COVID-19. Both IFN-κ and TFF2 are small proteins that can be induced to respond to respiratory virus infections. According to various test data, the performance of patients in the IFN-κ+TFF2 group is more stable in all aspects, and inflammation is reduced. Aerosol inhalation is a non-invasive and easy-to-use method for patients. It is also suitable for delivery to COVID-19 patients with ventilator through an oxygen tube. Our clinical investigation shows that there is no discomfort during the inhalation process.
The subjects recruited this time are all moderate COVID-19 cases, and it is not clear whether this treatment is applicable to severe cases. But preliminary studies have shown that IFN-κ+TFF2 may be a safe treatment method and beneficial to COVID-19 patients. In order to further determine its efficacy against COVID-19, the scale of research needs to be further expanded. The treatment method of aerosol inhalation of IFN-κ+TFF2 is likely to improve clinical treatment, thereby shortening the patient’s hospital stay.
Inhalation preparations are also unique in terms of technology development and review and approval. It is necessary to comprehensively consider the product’s prescription technology, quality control, drug delivery device, industrial production, and clinical application. Medicilon is familiar with the development process of various inhalation preparations, especially in the field of inhalation powder inhalation (DPI), atomized inhalation and nasal spray (Nasal Spray) preparations. It has very rich research and development experience and is equipped with professional equipment, such as COPLEY’s new generation of medicinal impactor (NGI), COPLEY’s BRS2100 breathing simulator, Germany’s Sinpatek laser particle size analyzer, etc., can meet the quality research and in vitro evaluation of various inhalation preparations.
Medicilon has a complete preclinical research platform for inhaled drug delivery, including pharmacokinetic tests and efficacy tests of inhaled drugs; at the same time, it can complete the safety evaluation of a complete set of drugs, such as tissue distribution test, acute toxicity test, repeated administration toxicity test , Irritation test, allergy test and safety pharmacology test, etc. Medicilon will continue to pay attention to the progress of this research. This is destined to be a “protracted war” that all mankind will fight against. However, we believe that one day we will overcome the epidemic and the world will be safe.
More articles on “COVID-19 Drug Development”
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